Supplementary Material for: Bevacizumab related gastrointestinal perforation in Hepatocellular Carcinoma patient: A Case Report

Introduction: Atezolizumab plus bevacizumab is widely recognized as the first-line treatment for advanced hepatocellular carcinoma (HCC). Bevacizumab, an anti-vascular endothelial growth factor (anti-VEGF), is effective against various cancers but carries a rare risk of gastrointestinal perforation. The exact mechanism remains unclear, but insufficient cessation before surgery is a significant factor. We report a case of gastric perforation after hepatectomy in a patient with HCC who had previously received atezolizumab–bevacizumab combination therapy. Despite discontinuation of bevacizumab for five weeks before surgery, the patient developed gastric perforation on postoperative day six. Case: A 62-year-old female with Hepatitis B virus-related HCC and a history of liver wedge resection and cholecystectomy presented with elevated α-fetoprotein (AFP) levels and imaging-confirmed recurrent HCC with tumor thrombosis. She underwent systemic therapy with atezolizumab and bevacizumab, achieving downstaging after six courses. Exploratory laparotomy with left liver lobectomy was performed. Postoperatively, the patient developed fever, elevated C-reactive protein(CRP), and turbid peri-hepatic drainage fluid. Gastric perforation was diagnosed after series examination. Emergent laparotomy with primary repair was performed and the patient recovered uneventfully. Discussion: Bevacizumab-associated gastrointestinal perforation, with an incidence of 0.3–2.4%, is a rare but severe complication. Proposed mechanisms include prothrombotic effects causing vessel thrombosis, impaired wall healing due to VEGF inhibition, reduced blood flow to the intestinal wall, and tumor destruction leading to wall instability. Bevacizumab also hinders surgical repair healing. Conclusions: This case highlights the importance of individualized perioperative management and careful timing of surgery following anti-VEGF therapy in HCC, emphasizing the role of multidisciplinary evaluation in the era of immunotherapy and targeted treatment.